8-hydroxyquinoline acetamide compound, 8-hydroxy quinoline thioamide compound and use thereof

ABSTRACT

Disclosed are a novel 8-hydroxyquinoline acetamide compound, an 8-hydroxyquinoline thioamide and use thereof. More specifically, disclosed are a novel 8-hydroxyquinoline thioamide compound suitable for use as a selective chemodosimeter that shows considerably high detection sensitivity to mercury ions, an 8-hydroxyquinoline acetamide compound as an intermediate thereof, preparation thereof, and a chemodosimeter for mercury ion-selective detection, the chemodosimeter comprising the 8-hydroxyquinoline thioamide compound. The compounds as disclosed herein exhibit considerably effective fluorescence specificity of an off-on type, detect a micromole of mercury ions from chemical and biological aqueous systems, and allow 100% desulfurization within 5 minutes, thus being considerably useful in the chemical industry.

This non-provisional application claims priority to Korean PatentApplication No. 10-2006-0077550, filed on Aug. 17, 2006, and all thebenefits accruing therefrom under 35 U.S.C. §119(a) on, the content ofwhich is herein incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a novel 8-hydroxyquinoline acetamidecompound, an 8-hydroxyquinoline thioamide and use thereof. Morespecifically, the present invention relates to a novel8-hydroxyquinoline thioamide compound suitable for use as a selectivechemodosimeter that shows considerable high detection sensitivity tomercury ions, an 8-hydroxyquinoline acetamide compound as anintermediate thereof, preparation thereof, and mercury ion-selectivedetection using the same.

2. Description of the Related Art

As used herein, the term “chemodosimeter” refers to a detection systemthat detects metal cations as a detection target via a chemicalreaction, i.e. stoichiometric reaction. There are some differencesbetween the chemodosimeter and the chemical sensor. Firstly, thechemodosimeter must react stoichiometrically with the target metal,whereas the chemical sensor interacts with the target in a veryselective or specific way. Secondly, expression of specific fluorescentproperties is irreversible which results from the structural changes ofthe chemodosimeter through the chemical reaction. In other words, oncethe chemical change undergone, the chemodosimeter does not return to aninitial state in the same reaction system. In contrast, as the chemicalsensor emits fluorescence via binding with the metal cations (withoutchemical changes), the thus-bound cations can be eliminated with the useof a strong chelating agent such as EDTA. Therefore, the chemical sensorinvolves a reversible process.

Recently, a great deal of research has been conducted to developchemodosimeters and chemical sensors for use in selective and efficientdetection of chemically or biochemically important ionic materials. Ithas been known that the most desirable technique to develop sensorsselective and sensitive for a specific material is the use of awell-known and efficient binding site coupled with a suitable signalingsubunit. In particular, various fluorescent functional groups have beenintroduced as the signaling subunit. This is because fluorescentfunctional groups have high sensitivity and easy signal-convertibility.

Various selective fluorescent chemodosimeters have been reported todate. For example, fluorescent-sensitive properties selective formercury ions involved in desulfurization was reported by (a) Chae,M.-Y.; Czarnik, A. W. J. Am. Chem. Soc. 1992, 114, 9704. (b) Yang, Y.K.; Yook, K. J.; Tae, J. J. Am. Chem. Soc. 2005, 127, 16760. (c) Zhang,G.; Zhang, D.; Yin, S.; Yang, X.; Shuai, Z.; Zhu, D. Chem. Commun. 2005,2161. In particular, Chae et. al., suggested a9-[(methyl-amino)thiocarbonyl]anthracene compound serving as achemodosimeter that expresses changes in the fluorescence emissionbehavior which results from desulfurization by mercury and silver ions.However, there remain problems in that the compound is selective forboth mercury ions and silver ions and incomplete desulfurization (e.g.87%) is carried out after 10 min.

Furthermore, a selective fluorescent variation for copper ions (Cu²⁺)was reported by Dujols, V.; Ford, F.; Czarnik, A. W. J. Am. Chem. Soc.1997, 119, 7386. Optically electrochemically sensitive properties forheavy metals such as mercury (Hg²⁺), lead (Pb²⁺) and cadmium (Cd²⁺) werereported by (a) Takahashi, Y.; Kasai, H.; Nakanishi, H.; Suzuki, T. M.Angew. Chem., Int. Ed. 2006, 45, 913, (b) Oehme, I.; Wolfbeis, O, S.Mikrochim. Acta 1997, 126, 177, (c) Bonfil, Y.; Brand, M.;Kirowa-Eisner, E. Anal. Chim. Acta 2002, 464, 99, etc. A selectivefluorescent sensitive properties for alkali metal ions and alkalineearth metal ions was reported by (a) Kollmannsberger, M.; Rurack, K.;Resch-Genger, U; Rettig, W; Daub, J. Chem. Phys. Lett. 2000, 329, 363,(b) Rurack, K; Sczepan, M.; Spieles, M.; Resch-Genger, U.; Rettig, W.Chem. Phys. Lett. 2000, 320, 87, etc.

Meanwhile, toxicity of mercury ions was well-known in environmentalfields, and continuous development for various sensors capable ofsensitively and selectively detecting mercury ions under variousconditions have been thus made in the fields. The sensors necessarilyexhibit significant variation in spectroscopic properties in response tobinding to mercury ions. The use of fluorescent properties for thesensors is based on ease of quantitative analysis or signal conversion.

However, the fore-mentioned methods for detecting metal ions, inparticular, chemodosimeters exhibiting a selective fluorescentsensitivity for mercury ions involved in desulfurization have someproblems in that it takes a long time to increase fluorescence intensityin response to desulfurization or has low detection sensitivity becauseof an insufficient increase in the level of fluorescence intensity, whencompared to the value prior to desulfurization. Furthermore, there is alimitation on exclusive detection of mercury ions because of undesireddetection of other ions (e.g. silver ions) in addition to mercury ions.

BRIEF SUMMARY OF THE INVENTION

Exemplary embodiments of the present invention have been made in view ofthe problems of the prior art, and in one embodiment, a novel8-hydroxyquinoline thioamide compound suitable for use as mercuryions-selective chemodosimeter that has considerable high detectionsensitivity to mercury ions, an 8-hydroxyquinoline acetamide compound asan intermediate thereof and preparation thereof are provided.

In another embodiment, a chemodosimeter for selective detection ofmercury ions which comprises an 8-hydroxyquinoline thioamide compoundrepresented by Formula 3 and a method for selectively detecting mercuryions using the chemodosimeter are provided.

In accordance with one embodiment, there is provided an8-hydroxyquinoline acetamide compound represented by Formula 2 below:

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.

Preferably, the compound of Formula 2 may be2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylacetamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dimethylacetamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dipropylacetamide, or2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dibutylacetamide.

In accordance with another embodiment, there is provided an8-hydroxyquinoline thioamide compound represented by Formula 3 below:

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.

Preferably, the compound of Formula 3 may be2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylethanethioamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dimethylethanethioamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dipropylethanethioamide,or2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dibutylethanethioamide.

In accordance with another embodiment, there is provided a method forpreparing an 8-hydroxyquinoline acetamide compound by reacting an8-hydroxyquinoline compound represented by the following Formula 1 with2-chloro-N,N-diethylacetamide, potassium carbonate and potassium iodidein an organic solvent under an inlet gas atmosphere.

wherein X is S, O or NH.

Preferably, the molar ratio of the 8-hydroxyquinoline compound ofFormula 1, 2-chloro-N,N-diethylacetamide, potassium carbonate andpotassium iodide may be 1:1.2-2.0:1.0-2.0:0.05-0.2

The organic solvent may be tetrahydrofuran (THF).

In accordance with another embodiment, there is provided a method forpreparing an 8-hydroxyquinoline thioamide compound represented by thefollowing Formula 3 by reacting the 8-hydroxyquinoline acetamidecompound of Formula 2 with a Lawesson's reagent in an organic solvent.

In preparation of the 8-hydroxyquinoline thioamide compound of Formula3, the molar ratio of the 8-hydroxyquinoline acetamide compound to theLawesson's reagent may be preferably 1:1.0-1.5. The organic solvent maybe preferably toluene.

In accordance with another embodiment, there is provided a method forsynthesizing an 8-hydroxyquinoline thioamide compound with selectivityfor mercury ions as depicted in the following Reaction Scheme 1, themethod comprising:

1) reacting an 8-hydroxyquinoline compound 1 represented by thefollowing Formula 1 with 2-chloro-N,N-diethylacetamide, potassiumcarbonate and potassium iodide in an organic solvent under an inlet gasatmosphere to prepare an 8-hydroxyquinoline acetamide compoundrepresented by Formula 2; and

2) reacting the 8-hydroxyquinoline acetamide compound with Lawesson'sreagent in an organic solvent to prepare an 8-hydroxyquinoline thioamidecompound represented by the following Formula 3.

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.

In accordance with another embodiment, there is provided achemodosimeter for mercury ion-selective detection, the chemodosimetercomprising the 8-hydroxyquinoline thioamide compound of Formula 3.

In accordance with yet another embodiment, there is provided a methodfor selectively detecting mercury ions, the method comprising:

dissolving the 8-hydroxyquinoline thioamide compound of Formula 3 inwater, acetonitrile, or a mixed solvent of water and acetonitrile;

adding a desired reagent to the solution; and

detecting mercury ions by analyzing a fluorescence spectrum involved indesulfurization of mercury ions contained in the reagent with the8-hydroxyquinoline thioamide compound, as depicted in the followingReaction Scheme 2:

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.

Preferably, water and acetonitrile of the mixed solvent may be used in aratio of 1:99-99:1.

The minimum detectable concentration of mercury ions may be 5.4×10⁻⁷ M.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other features and advantages of the present inventionwill be more clearly understood from the following detailed descriptiontaken in conjunction with the accompanying drawings, in which:

FIG. 1 is a ¹H-NMR spectrum of an 8-hydroxyquinoline compoundrepresented by Formula 1 according to the present invention;

FIGS. 2 a and 2 b are a ¹H-NMR spectrum and a ¹³C-NMR spectrum of an8-hydroxyquinoline acetamide compound represented by Formula 2 accordingto the present invention, respectively;

FIGS. 3 a and 3 b are a ¹H-NMR spectrum and a ¹³C-NMR spectrum of an8-hydroxyquinoline thioamide compound represented by Formula 3 accordingto the present invention, respectively;

FIG. 4 is a ¹H-NMR spectral graph illustrating conversion of an8-hydroxyquinoline thioamide compound of Formula 3 into an8-hydroxyquinoline acetamide compound of Formula 2, which results fromdesulfurization by addition of mercury ions according to the presentinvention;

FIG. 5 is a fluorescence spectrum illustrating an 8-hydroxyquinolinethioamide compound of Formula 3 of the present invention according tothe type of metal ions;

FIG. 6 is a fluorescence spectrum illustrating an 8-hydroxyquinolinethioamide compound of Formula 3 of the present invention as a functionof a mercury ion concentration;

FIG. 7 is a fluorescence spectrum illustrating an 8-hydroxyquinolinethioamide compound of Formula 3 of the present invention according tomercury ions and EDTA;

FIG. 8 is a fluorescence spectrum illustrating sensitivity of an8-hydroxyquinoline thioamide compound of Formula 3 of the presentinvention for mercury ions in a system containing a great amount ofphysiologically important metal ions as a function of a mercury ionconcentration;

FIG. 9 a is a fluorescence spectrum illustrating a detection result ofmetal ions under a Tris buffer solution after dissolving an8-hydroxyquinoline thioamide compound of Formula 3 of the presentinvention in a mixed solvent of methanol and water (9:1, v/v), and FIG.9 b is a fluorescence spectrum illustrating a detection result of metalions under an acetate buffer solution; and

FIG. 10 a is a fluorescence spectrum illustrating a detection result ofmetal ions under a Hepes buffer solution after dissolving an8-hydroxyquinoline thioamide compound of Formula 3 of the presentinvention in a mixed solvent of dioxane and water (9:1, v/v), and FIG.10 b is a fluorescence spectrum illustrating a detection result of metalions under an acetate buffer solution.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention will now be described in greater detail withreference to the accompanying drawings.

In one aspect, the present invention is directed to a novel8-hydroxyquinoline thioamide compound of Formula 3, which has astructure where benzo[d]thiazol and N,N-diethylethanethioamide moietiesare introduced into an 8-hydroxyquinoline skeleton, imparting selectivefluorescence enhancement for highly toxic mercury ions to the compoundfor easy and selective detection of mercury, and a novel8-hydroxyquinoline acetamide compound represented by Formula 2 as anintermediate thereof.

A more detailed explanation of the 8-hydroxyquinoline acetamide compoundrepresented by the following Formula 2 will be given below:

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.

The 8-hydroxyquinoline acetamide compound of Formula 2, which is anintermediate of a novel 8-hydroxyquinoline thioamide compoundrepresented by Formula 3, is prepared from a well-known8-hydroxyquinoline compound represented by Formula 1 as a startingmaterial. A detailed explanation for preparation thereof will be givenin the related section.

wherein X is S, O or NH.

Specific examples of the compound of Formula 2 include2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylacetamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dimethylacetamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dipropylacetamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dibutylacetamide andmixtures thereof.

The compound of Formula 2 is considered significant in that it is anintermediate of the compound of Formula 3 which actually serves as achemodosimeter, but is stable and is restorable from the compound ofFormula 3 via desulfurization caused by reaction of the compound ofFormula 3 with mercury ions, as depicted in the following ReactionScheme 1.

Then, a more detailed explanation of the 8-hydroxyquinoline thioamidecompound represented by Formula 3 will be given below:

wherein X is S, Q or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.

The 8-hydroxyquinoline thioamide compound of Formula 3 is a novelcompound capable of selectively detecting mercury ions only. Thecompound of Formula 3 can be prepared from the 8-hydroxyquinolineacetamide compound of Formula 2, but is not particularly limited to thiscompound.

The 8-hydroxyquinoline thioamide compound of Formula 3 has a structurewhere benzo[d]thiazol and N,N-diethylethanethioamide moieties areintroduced into an 8-hydroxyquinoline skeleton, allowing selectivefluorescence enhancement for mercury ions which are of considerableimportance in environmental fields and are severely toxic for thepurpose of easily detecting the mercury ions exclusively.

Specific examples of the compound of Formula 3 include2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylethanethioamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dimethylethanethioamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dipropylethanethioamideand2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dibutylethanethioamideand mixtures thereof.

The 8-hydroxyquinoline thioamide compound of Formula 3 is used as achemodosimeter for selectively detecting mercury ions. The detectionmethod using the compound 3 will be explained as follows.

First, the 8-hydroxyquinoline thioamide compound of Formula 3 isdissolved in water, acetonitrile or a mixture thereof as a solvent. In acase where a mixture of water and acetonitrile is used as a solvent, amixed ratio of water and acetonitrile is not particularly limited. Aconcentration of the 8-hydroxyquinoline thioamide compound in thesolvent is preferably adjusted to 1.0×10⁻⁶ M to 2×10⁻⁵ M.

The use of water, acetonitrile or a mixture thereof as a solvent isnecessary for specific detection of mercury ions. The use of othersolvents instead of these solvents causes an increase in reactivity ofthe 8-hydroxyquinoline thioamide compound to other metal ions as well asmercury ions, thus making it difficult to use the compound as aselective chemodosimeter.

Then, a desired reagent is added to the 8-hydroxyquinoline thioamidecompound solution. The reagent may be body fluids for measurement of thecontamination level of purified water or sewage, or confirmatory testfor mercury poisoning in the human body, but is not particularly limitedthereto.

Mercury ions can be detected by measuring a fluorescence spectrum whichresults from desulfurization of mercury ions in the reagent with the8-hydroxyquinoline thioamide compound, as depicted in the followingReaction scheme 2. In this case, a minimum detectable concentration ofmercury ions is 5.4×10⁻⁷ M. Accordingly, the chemodosimeter according tothe present invention is different from general chemodosimeters fordetection of mercury ions in that it can detect mercury ions evenalthough an extremely small amount of the mercury ions are contained inthe reagent.

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.

The reason for the selective fluorescence enhancement of the compound ofFormula 3 is that a thioamide group of the compound 3 is converted to anamide group via a chemical reaction of the compound 3 with mercury ions.The conversion of the compound of Formula 3 into the compound of Formula2, as depicted in Reaction Scheme 2, can be confirmed from the testresults shown in FIGS. 6 to 8.

The reaction is carried out by hydrolysis of a thioamide group into anamide group. In particular, the hydrolysis is known to be facilitated bysome metal ions acting as catalysts. In this case, sulfur atoms removedby the hydrolysis are reacted with metal ions to form metal sulfide. Thepresent invention is designed such that mercury ions only act as aspecific catalyst rather than other metal ions. In addition, the presentinvention suggests optimal conditions for fluorescence signaling of thecompound to mercury ions via systematic experiments in accordance withvarious reaction conditions.

Mercury analysis according to the present invention can be utilized inapplications including: measurement of the degree of mercurycontamination in drinking water (e.g., public water and groundwater)according to drinking water criterion; measurement of the concentrationof mercury in high-concentration contaminants-containing water includingindustrial water or industrial sewage; and measurement of the degree ofmercury contamination in foods including beverages, fish or shellfish.

Subsequently, a method for preparing the 8-hydroxyquinoline acetamidecompound of Formula 2 will be mentioned in detail.

First, a more detailed explanation of preparation of an8-hydroxyquinoline compound represented by the following Formula 1,which is a starting material of the 8-hydroxyquinoline acetamidecompound of Formula 2, will be given below:

wherein X is S, O or NH.

The 8-hydroxyquinoline compound of Formula 1 is synthesized by reacting8-hydroxyquinoline-2-carboxylic acid with 2-aminothiophenol andphosphorus trichloride (PCl₃) in toluene, as depicted in the followingReaction 3. 2-Aminothiophenol is used to prepare a compound where “X” inthe Formula 1 is sulfur (S). To prepare a compound where “X” in theFormula 1 is O or NH, another suitable reagent may be used. Morespecifically, when X is oxygen (O), 8-hydroxyquinoline-2-carboxylic acidis reacted with 2-aminophenol and 8-hydroxyquinoline-2-carboxylic acidin polyphosphoric acid as a solvent. When X is NH,8-hydroxyquinoline-2-carboxylic acid is reacted with manganese (III)acetate (Mn(OAc)₃) 1,2-diaminobenzene and8-hydroxyquinoline-2-carboxaldehyde in acetic acid.

An 8-hydroxyquinoline acetamide compound of Formula 2 is prepared byreacting the 8-hydroxyquinoline compound of Formula 1,2-chloro-N,N-diethyl acetamide, potassium carbonate and potassium iodidein an organic solvent under an inlet gas atmosphere.

Preferably, the molar ratio of the 8-hydroxyquinoline compound ofFormula 1, 2-chloro-N,N-diethyl acetamide, potassium carbonate andpotassium iodide is 1:1.2-2.0:1.0-2.0:0.05-0.2.

Tetrahydrofuran (THF) may be used as the organic solvent.

First, a method for preparing an 8-hydroxyquinoline thioamide compoundof Formula 3 will be mentioned in detail below:

In one aspect, the present invention is directed to a method forpreparing an 8-hydroxyquinoline thioamide compound represented byFormula 3 by reacting the 8-hydroxyquinoline acetamide compound ofFormula 2 with a Lawesson's reagent in an organic solvent.

In preparation of the 8-hydroxyquinoline thioamide compound of Formula3, the molar ratio of the 8-hydroxyquinoline acetamide compound ofFormula 2 to the Lawesson agent may be preferably 1:1.0-1.5, morePreferably, 1:1. The organic solvent may be preferably toluene.

In summary, the method for synthesizing an 8-hydroxyquinoline thioamidecompound of Formula 3 depicted in the following Reaction Scheme 1comprising the steps:

1) reacting an 8-hydroxyquinoline compound 1 represented by thefollowing Formula 1, 2-chloro-N,N-diethyl acetamide, potassium carbonateand potassium iodide in an organic solvent under an inlet gas atmosphereto prepare an 8-hydroxyquinoline acetamide compound represented byFormula 2; and

2) reacting the 8-hydroxyquinoline acetamide compound of Formula 2 witha Lawesson's reagent in an organic solvent to prepare an8-hydroxyquinoline thioamide compound represented by Formula 3.

wherein X is S, Q or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.

By introducing hydroxyquinoline as a well-known binding site,benzo[d]thiazol and N,N-diethylethanethioamide serving as both asignaling site and an additional binding site into the8-hydroxyquinoline thioamide compound of Formula 3 according to thepresent invention, selectivity for mercury ions is imparted to thecompound. Accordingly, the compound can be used as a selectivechemodosimeter for mercury ions.

In addition, the compound of Formula 3 of the present invention can showeffective fluorescence specificity of an off-on type and detect amicromole of mercury ions from chemical and biological aqueous systems,and allows 100% desulfurization within 5 minutes, thus realizingsuperior detection sensitivity and reduced detection time, as comparedto conventional chemodosimeters for detection of mercury ions.

Hereinafter, the present invention will be explained in more detail withreference to the following examples. However, these examples are givenfor the purpose of illustration and are not to be construed as limitingthe scope of the invention.

EXAMPLES Synthesis Example Synthesis of2-(benzo[d]thiazol-2-yl)quinolin-8-ol

To introduce a benzo[d]thiazol group into an 8-hydroxyquinolinecompound, 2-aminothiophenol (123 mg, 1.1 mmol) and8-hydroxyquinoline-2-carboxylic acid (189 mg, 2 mmol) were dissolved indry toluene (30 ml) with blown nitrogen to prevent oxidation which iscaused by oxygen in air. The solution was heated to 40° C. andphosphrous trichloride (0.1 ml, 1.1 mmol) was slowly added thereto.Then, the reaction solution was heated at 100° C. for 24 hours andallowed to cool. The reaction mixture was extracted with a 20% aqueoussodium carbonate solution, distilled water and dichloromethane, driedand recrystallized with dichloromethane and hexane to yield2-(benzo[d]thiazol-2-yl)quinolin-8-ol, the compound of Formula 1 as alight green solid (yield: 75%).

The 2-(benzo[d]thiazol-2-yl)quinolin-8-ol is an 8-hydroxyquinolinecompound represented by Formula 1 and has a melting point of 189° C. to191° C. As can be seen from FIG. 1, the NMR result and elementalanalysis result of the compound are as follows:

¹H NMR (CDCl₃, 300 MHz) δ 8.51 (d, J=8.7 Hz, 1H), 8.32 (d, J=8.7 Hz,1H), 8.16 (d, J=8.1 Hz, 1H), 8.05 (s, 1H), 7.99 (d, J=8.1 Hz, 1H),7.54-7.24 (m, 4H), 7.24 (d, J=7.5 Hz, 1H); ¹³C NMR (75 MHz, CDCl₃)δ152.5, 137.5, 129.5, 129.3, 126.7, 126.3, 124.1, 119.3, 118.3, 111.2;HRMS (EI); m/z calcd for C₁₆H₁₀N₂OS 278.0514. Found 278.0478.

Example 1 Synthesis of2-(2-(benzo[d]thiazol-2-yl)quinolin-8-yloxy)-N,N-diethylacetamide

The N,N-diethylacetamide prepared in Synthesis Example (278 mg, 1 mmol),potassium carbonate (K₂CO₃, 276 mg, 2 mmol) and potassium iodide (KI, 17mg, 1.5 mmol) were stirred in tetrahydrofuran with blown nitrogen toprevent oxidation which is caused by oxygen in air. Then,2-chloro-N,N-diethylacetamide (225 mg, 1.5 mmol) was added to themixture. The resulting mixture was stirred at 80° C. for 26 hours andextracted with dichrolomethane and distilled water. The obtainedextracts were dried and purified by column chromatography (hexane:ethylacetate=1:1, v/v) to yield a yellow solid of the compound 2 (yield:63%).

As can be seen from FIGS. 2 a and 2 b, the NMR result and elementalanalysis result of the compound 2 are as follows:

¹H NMR (CDCl₃, 300 MHz) 8.51 (d, J=14.5 Hz, 1H), 8.29 (d, J=14.5 Hz,1H), 8.14 (dd, J=11 Hz and 1.5 Hz, 1H), 7.99 (dd, J=11 and 1.5 Hz, 1H),7.54-7.45 (m, 4H), 7.3-7.28 (m, 1H), 5.10 (s, 2H), 3.63 (q, J=11.5 Hz,2H), 3.45 (q, J=11.5 Hz, 2H), 1.25 (t, J=12 Hz, 3H), 1.18 (t, J=11.7 Hz,3H). ¹³C NMR (CDCl₃, 75 MHz) 170.4, 167.4, 154.7, 154.2, 150.4, 140.3,137.3, 136.8, 130.6, 128.3, 126.5, 126.1, 124.0, 122.3, 121.1, 119.0,112.4, 69.6, 42.1, 40.4, 14.6, 12.9. HRMS (EI) Calcd for C₂₂H₂₁N₃O₂S,391.1354. Found 391.1356.

As a result, the compound 2 is confirmed to be2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylacetamide asone of compounds that can be represented by Formula 2.

Example 2 Synthesis of2-(2-benzo[d]thiazol-2-yl)quinolin-8-yloxy)-N,N-diethylethanethioamide

The 2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylacetamideprepared in Example 1 (196 mg, 0.5 mmol) was dissolved in dry toluene.To the solution was added Lawesson's reagent (203 mg, 0.5 mmol). Then,the mixture was heated at 100° C. for 36 hours and allowed to cool toobtain a solid. The solid was purified by column chromatography(hexane:ethyl acetate=3.5:1, v/v) to yield a white solid of the compound3 (yield: 62%).

As can be seen from FIGS. 3 a and 3 b, the NMR result and elementalanalysis result of the compound 3 are as follows:

¹H NMR (CDCl₃, 300 MHz) 8.52 (d, J=14.5 Hz, 1H), 8.29 (d, J=14 Hz, 1H),8.14 (d, J=11.5 and 1 Hz, 1H), 7.99 (dd, =1 and 12 Hz, 1H), 7.57-7.45(m, 5H), 5.47 (s, 2H), 4.05 (q, J=12 Hz, 2H), 4.00 (q, J=12.5 Hz, 2H),1.38 (t, J=11.7 Hz, 3H), 1.31 (t, J=11.8 Hz, 3H). ¹³C NMR (CDCl₃, 125MHz) 194.5, 170.2, 154.6, 153.8, 150.4, 140.2, 137.2, 136.7, 130.5,128.3, 126.5, 126.1, 124.0, 122.2, 121.1, 119.0, 112.9, 76.8, 48.1,48.0, 14.3, 11.0. HRMS (EI) Calcd for C₂₂H₂₁N₃OS₂, 407.1126. Found407.1125.

As a result, the compound 3 is confirmed to be2-(2-benzo[d]thiazol-2-yl)quinolin-8-yloxy)-N,N-diethylethanethioamideas one of compounds that can be represented by Formula 3.

Experimental Example 1 Test of Fluorescent Properties

The ionophoric properties of the2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylthioamidecompound prepared in Example 2 were evaluated by fluorescencespectroscopy. Specifically, it could be confirmed from preliminary testsin accordance with various solvent conditions that the compound'sbehavior was optimized under an aqueous acetonitrile solution and a Trisbuffer solution (pH=8.1) for the detection of metal ions in a biologicalreagent. Accordingly, tests herein were carried out under theseconditions.

The 2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylthioamidecompound exhibited a maximum adsorption band at 345 nm, and a very weakfluorescence at about 475 nm in an aqueous acetonitrile solution(excitation=345 nm, acetonitrile:water=30:70, v/v). Meanwhile, it couldbe seen from FIG. 4 that when the compound (represented by Formula 3,5.0×10⁻⁴ M) is reacted with a 100-fold concentration of metalperchlorate (where the metal is selected from: transition metalsincluding Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺ and Hg²⁺; alkali metals including Na⁺and K⁺; and alkaline earth metals including Mg²⁺ and Ca²⁺), significantfluorescence enhancement for Hg²⁺ only was observed.

Since the detection sensitivity of the2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylthioamidecompound for mercury was considerably excellent, even the use ofone-fold concentration of Hg²⁺ leaded to a 167-fold increase influorescence intensity at 479 nm, as compared to the case where there isno mercury ion. The use of Cd²⁺ only among these metal ions caused a3.8-fold increase in fluorescence intensity, and other metal ions causeda slight increase (i.e. 2-fold or less) in fluorescence intensity.

In addition, the signaling property of the2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylthioamidecompound was evaluated by fluorescence titration. While one-fold ofmercury ions was added, as mercury ions increased, fluorescenceintensity increased. However, when one or more-fold of mercury ions wasadded, an increase in fluorescence intensity was not observed any more.As a result of the fluorescence titration, the detection limit of the2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylthioamidecompound was obtained from a graph showing a variation in fluorescenceintensity as a function of a mercury ion concentration. The compoundcould be used to detect a micromole concentration of mercury ions in achemical or biological system as 5.4×10⁻⁷ M under a 30% aqueousacetonitrile solution (See FIG. 6).

Meanwhile, it is considered that mercury ion-selective fluorescenceenhancement of the2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylthioamidecompound is based on conversion of a thioamide group in the compound 3into an amide group, as depicted in the following Reaction Scheme 3:

The conversion of the compound 3 into the compound 2, shown in ReactionScheme 3, induced strong fluorescence emission. This phenomenon wasconfirmed from the results of EDTA experiments, NMR spectrum and Massspectrum.

More specifically, the addition of 100-fold concentration of mercuryions to the compound 3 leaded to great fluorescence enhancement. Then,the addition of 1.000-fold concentration of EDTA to the mixture causedno further variation. On the other hand, when a 100-fold concentrationof mercury ions was put in a system where the compound 3 and EDTAcoexist, EDTA having strongly chelating capability effectivelysequestered the mercury ions from interaction with the compound 3. Forthis reason, there was no variation in fluorescence intensity, which iscaused by desulfurization (See FIG. 7).

Then, the compound 3 was reacted with five-fold concentration of mercuryions in a 30% aqueous acetonitrile solution to obtain a product. Asapparent from FIG. 4, the product was confirmed to be the compound 2. Inaddition, it could be confirmed from mass spectrum that m/z of thecompound 3 was 391.1. Based on the fore-mentioned results, chemicalconversion of the compound 3 into the compound 2 by mercury ions wasconfirmed.

To confirm whether the compound of the present invention can be usedunder practical conditions for detection of mercury ions, sensitivity ofthe compound for mercury ions were evaluated in a system containing alarge amount of physiologically important metal ions ([Na⁺]=138 mM,[K⁺]=4 mM, [Mg²⁺]=1 mM, [Ca²⁺]=3 mM, [Zn²⁺]=0.02 mM, and [Cu²⁺]=0.015mM). As a result, it can be seen from FIGS. 5 and 8 that the compoundwas hardly affected by a large amount of other metal ions, when takinginto consideration the sensitivity and detection limit.

Meanwhile, the 8-hydroxyquinoline thioamide compound of Formula 3 wasdissolved in a mixed solvent of water and methanol, and a mixed solventof water and dioxane, respectively, instead of water, acetonitrile or amixture thereof, and the detection test of the solution for variousmetal ions was carried out by fluorescence spectroscopy. The result wasshown in FIGS. 9 a to 10 b. Accordingly, to selectively detect mercuryions only, as a solvent to dissolve the 8-hydroxyquinoline thioamidecompound, most preferred is to use of water, acetonitrile or a mixturethereof.

As apparent from the foregoing, by introduction of benzo[d]thiazol andN,N-diethylethanethioamide moieties serving as both a signaling site andan additional binding site into 8-hydroxyquinoline as a well-knownbinding site, the 8-hydroxyquinoline thioamide compound of Formula 3according to the present invention can exhibit specificity for mercuryions only. Accordingly, the compound can be used as a mercuryion-selective chemodosimeter.

In addition, the compound of Formula 3 of the present invention hasadvantages in that it can exhibit considerably effective fluorescencespecificity of an off-on type, detect a micromole of mercury ions fromchemical and biological aqueous systems, and allow 100% desulfurizationwithin 5 minutes, thus being considerably useful in the chemicalindustry.

Although the preferred embodiments of the present invention have beendisclosed for illustrative purposes, those skilled in the art willappreciate that various modifications, additions and substitutions arepossible, without departing from the scope and spirit of the inventionas disclosed in the accompanying claims.

1. An 8-hydroxyquinoline acetamide compound represented by Formula 2below:

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.
 2. The 8-hydroxyquinoline acetamide compoundaccording to claim 1, wherein the compound of Formula 2 is2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylacetamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dimethylacetamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dipropylacetamide, or2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dibutylacetamide. 3.An 8-hydroxyquinoline thioamide compound represented by Formula 3 below:

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.
 4. The 8-hydroxyquinoline thioamide compoundaccording to claim 3, wherein the compound of Formula 3 is2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-diethylethanethioamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dimethylethanethioamide,2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dipropylethanethioamide,or2-(2-(benzo[d]thiazol-2-yl)quinoline-8-yloxy)-N,N-dibutylethanethioamide.5. A method for preparing an 8-hydroxyquinoline acetamide compound byreacting an 8-hydroxyquinoline compound represented by the followingFormula 1 with 2-chloro-N,N-diethylacetamide, potassium carbonate andpotassium iodide in an organic solvent under an inlet gas atmosphere:

wherein X is S, O or NH.
 6. The method according to claim 5, wherein themolar ratio of the 8-hydroxyquinoline compound of Formula1,2-chloro-N,N-diethylacetamide, potassium carbonate and potassiumiodide is 1:1.2-2.0:1.0-2.0:0.05-0.2.
 7. The method according to claim5, wherein the organic solvent is tetrahydrofuran (THF).
 8. A method forpreparing a 8-hydroxyquinoline thioamide compound represented of Formula3 below:

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl, by reacting a 8-hydroxyquinoline acetamidecompound of Formula 2 below:

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl, with a Lawesson's reagent in an organicsolvent.
 9. The method for preparing an 8-hydroxyquinoline thioamidecompound according to claim 8, wherein the molar ratio of the8-hydroxyquinoline acetamide compound to the Lawesson's reagent is1:1.0-1.5 and the organic solvent is toluene.
 10. A method forsynthesizing an 8-hydroxyquinoline thioamide compound with selectivityfor mercury ions as depicted in the following Reaction Scheme 1, themethod comprising: 1) reacting an 8-hydroxyquinoline compound 1represented by the following Formula 1 with2-chloro-N,N-diethylacetamide, potassium carbonate and potassium iodidein an organic solvent under an inlet gas atmosphere to prepare an8-hydroxyquinoline acetamide compound represented by Formula 2; and 2)reacting the 8-hydroxyquinoline acetamide compound with Lawesson'sreagent in an organic solvent to prepare an 8-hydroxyquinoline thioamidecompound represented by the following Formula 3;

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.
 11. A chemodosimeter for mercury ion-selectivedetection, the chemodosimeter comprising the 8-hydroxyquinolinethioamide compound according to claim
 3. 12. A method for selectivelydetecting mercury ions, the method comprising: dissolving the8-hydroxyquinoline thioamide compound according to claim 3 in water,acetonitrile, or a mixed solvent of water and acetonitrile; adding adesired reagent to the solution; and detecting mercury ions by analyzinga fluorescence spectrum involved in desulfurization of mercury ionscontained in the reagent with the 8-hydroxyquinoline thioamide compound,as depicted in the following Reaction Scheme 2:

wherein X is S, O or NH; and R₁ and R₂ are each independently C_(1˜4)linear or branched alkyl.
 13. The method according to claim 12, whereinthe mixed ratio of water and acetonitrile are 1:99-99:1.
 14. The methodaccording to claim 12, wherein the minimum detectable concentration ofmercury ions is 5.4×10⁻⁷M.